High Ki‐67 proliferation index and lack of chemotherapy are associated with reduced overall survival in patients with triple negative breast cancer: a retrospective cohort in a major breast center in Hong Kong

89 Background: Ki-67 expression in breast cancer has been described as predictive of pathological complete response and prognostic of recurrence free survival (RFS). Our aim was to evaluate in a retrospective cohort of triple negative breast cancer patients if tumor proliferation measured by ki-67 expression is correlated with the outcome. Methods: We evaluated a retrospective cohort of 109 cases of triple negative breast cancer (ER-, PR- and HER2- determined by immunohistochemistry). Ki-67 labeling index was determined in Formalin-Fixed, Paraffin-Embedded residual tumors after neoadjuvant chemotherapy. Patients were stratified in Ki67<15% and Ki67≥15%. Clinicopathological data was retrieved from clinical records. RFS and overall survival (OS) were calculated using the Kaplan–Meier method and variables compared using the log-rank or Breslow test and Hazard Ratios (HR) estimated by the Cox regression. Results: The median age for patients was 47.5 years, 55 (50.5%) were premenopausal and 54 (49.5%) postmenopausal. Eight patients (7.3%) were clinical stages II and 101 (92.7%) stages III. Median of Ki-67 expression was 35.97% (0.96% - 77.7%). There was not association between Ki-67 expression (<15% VS ≥15%) with tumor size, nodal involvement, clinical stage and menopausal status. After a median of follow of 21.6 months, 62 patients (56.9%) have relapsed and 53 (48.6%) have die. The median time for RFS and OS were 21.2 and 31.4 months, respectively. Median of RFS was 12.6 months for Ki67<15% vs 21.2 months for Ki67≥15%, P=0.421 (HR=0.91). Median of OS was 34.9 months for Ki67<15% vs 31.4 months for Ki67≥15%, P=0.755 (HR=1.18). Only nodal involvement was found predictor of shorter RFS (0 nodes, 25.2 months vs 1 -3 nodes, 26.1 months, vs >3 nodes, 9.4 months, P=0.020). Conclusions: Ki-67 labeling index was not related with the outcome in terms of OS and RFS in patients with residual triple negative breast tumors that were treated with neoadjuvant chemotherapy.

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Clinical Implications of Androgen-Positive Triple-Negative Breast Cancer

Cancers ◽

10.3390/cancers13071642 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1642

Author(s):

Maša Brumec ◽

Monika Sobočan ◽

Iztok Takač ◽

Darja Arko

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Histological Grade ◽

Proliferation Index ◽

Clinical Implications ◽

Ki 67 ◽

Vast Array ◽

Node Metastasis ◽

Breast Cancer Subgroup

This review summarizes the recent findings of a vast array of studies conducted on androgen receptor-positive triple-negative breast cancer (AR-positive TNBC) to provide a better understanding of this specific breast cancer subgroup. AR expression is correlated with higher age, lower histological grade, lower proliferation index Ki-67, spiculated masses, and calcifications on mammography. Studies investigating the correlation between AR expression and lymph node metastasis are highly discordant. In addition, results regarding prognosis are highly contradictory. AR antagonists are a promising novel therapeutic approach in AR-positive TNBC. However, AR signaling pathways should be more investigated in order to understand the influence of AR expression on TNBC more thoroughly.

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Expression and prognostic significance of ECT2 in invasive breast cancer

Journal of Clinical Pathology ◽

10.1136/jclinpath-2017-204569 ◽

2017 ◽

Vol 71 (5) ◽

pp. 442-445 ◽

Cited By ~ 16

Author(s):

Hong-kun Wang ◽

Jian-fang Liang ◽

Hui-xia Zheng ◽

Hong Xiao

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Triple Negative ◽

Prognostic Significance ◽

High Expression ◽

Proliferation Index ◽

Ki 67 ◽

Node Metastasis

AimsTo investigate the expression of epithelial cell transforming sequence 2 (ECT2) in invasive breast cancer and its prognostic significance.MethodsECT2 immunohistochemical detection was performed in 165 breast cancer specimens and 100 normal control tissues. Univariable and multivariable Cox proportional hazards regression model analysis was used to confirm independent prognostic factors. The PHREG procedure linear hypotheses testing method was used to analyse survival data.ResultsExpression of ECT2 in breast cancer was significantly higher than that of the normal control group (p<0.001), and it was related to tumour grade, the status of lymph node metastasis, TNM staging, recurrence status, menopausal status, and the Ki-67 proliferation index (p<0.05), and not related to age, tumour size, tumour type, expression of estrogen receptor, progesterone receptor and human epidermal growth factor 2, and triple-negative disease (p>0.05). Univariable analysis showed that expression of ECT2, the status of lymph node metastasis, triple-negative disease and Ki-67 proliferation index were related to the overall survival of patients with breast cancer (p<0.001, p=0.006, p=0.001, p=0.041, respectively). PHREG procedure linear hypotheses testing results for overall survival revealed that high expression of ECT2, lymph node metastasis, triple-negative disease and high Ki-67 proliferation index predicted lower overall survival rates. Multivariable Cox regression indicated that high expression of ECT2 and triple-negative disease were independent prognostic factors for patients with breast cancer (p<0.001, p=0.004, respectively).ConclusionsExpression of ECT2 may be one of the main causes of the occurrence and development of breast cancer, and high expression of ECT2 as an independent prognostic factor predicts a poor prognosis. ECT2 could also be a potential molecular target for designing therapeutic strategies for breast cancer.

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Prognostic value of vitamin D receptor and insulin-like growth factor receptor 1 expression in triple-negative breast cancer

Journal of Clinical Pathology ◽

10.1136/jclinpath-2016-204222 ◽

2017 ◽

Vol 71 (1) ◽

pp. 34-39 ◽

Cited By ~ 6

Author(s):

Martina Soljic ◽

Ivana Mrklic ◽

Snjezana Tomic ◽

Tomislav Omrcen ◽

Nikica Sutalo ◽

...

Keyword(s):

Breast Cancer ◽

Vitamin D ◽

Overall Survival ◽

Growth Factor ◽

Vitamin D Receptor ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Growth Factor Receptor ◽

Insulin Like Growth Factor ◽

Ki 67

AimTriple-negative breast cancer (TNBC) is characterised by shorter overall survival and an early peak of distant recurrences with still no specific targeted treatment available. Vitamin D receptor (VDR) and insulin-like growth factor receptor 1 (IGFR) have recently been described as potential new targets for anticancer therapy, yet their roles in TNBCs are still to be explored. In this study we investigated VDR and IGFR expression in patients with TNBC and compared them with clinical and pathological parameters and survival to possibly demonstrate their prognostic and therapeutic relevance.MethodsThe study included 96 patients with TNBC. Clinical and pathological parameters were compared with the immunohistochemical expression of VDR and IGFR.ResultsPositive VDR immunostaining was present in 27% of tumours and inversely correlated with higher mitotic score, histological grade and higher proliferation index measured by Ki-67 and related to the increased overall survival (OS). Out of 96 patients with TNBC, 35.5% of tumours were IGFR positive and correlated with higher mitotic score and Ki-67, and strongly correlated with shorter disease-free survival (DFS). Patients with VDR-negative and IGF-positive tumours had significantly lower DFS and OS.ConclusionApproximately one third of TNBCs express VDR and/or IGFR. Their expression is linked with the recurrence of the disease and survival, which make them possible targets for treatment and a prognostic tool for dividing TNBCs into more homogeneous subgroups.

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Applicability of PD-L1 tests to tailor triple-negative breast cancer treatment in Brazil

Surgical and Experimental Pathology ◽

10.1186/s42047-021-00092-5 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Kátia Ramos Moreira Leite ◽

Carlos Henrique Barrios ◽

Antônio Carlos Buzaid ◽

Débora Gagliato ◽

Helenice Gobbi ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Triple Negative Breast Cancer ◽

Median Overall Survival ◽

Triple Negative ◽

Breast Cancer Treatment ◽

Main Text ◽

Critical Questions ◽

Online Panel ◽

Active Interest

Abstract Background Triple-negative breast cancer (TNBC) is a heterogeneous disease that represents 10–20% of breast cancer cases. The prognosis for advanced TNBC is usually poor, with a median overall survival of approximately 18 months or less. Main text New targeted therapies such as anti-PD-L1 agents are emerging as an option to treat advanced TNBC. A panel of 6 national experts with an active interest in breast cancer convened online. Panel members had either clinical or pathology experience in breast cancer. The experts pre-defined critical questions in the management of PD-L1 in TNBC, and a literature review was performed for selected topics before the online meeting. Conclusion The experts led active discussions involving a multidisciplinary team comprising pathologists and clinical oncologists. The meeting served to discuss the most relevant issues. A total of 10 critical questions for PD-L1+ TNBC were debated and are presented in this review. This article discusses the current landscape for PD-L1 tests in TNBC in Brazil.

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Distinct Somatic Alteration Features Identified by Gene Panel Sequencing in Korean Triple-Negative Breast Cancer with High Ki67 Expression

Diagnostics ◽

10.3390/diagnostics11030416 ◽

2021 ◽

Vol 11 (3) ◽

pp. 416

Author(s):

Woo Young Sun ◽

Jina Lee ◽

Bong Kyun Kim ◽

Jong Ok Kim ◽

Joonhong Park

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Hormone Receptor ◽

Mutation Frequency ◽

Triple Negative ◽

Genetic Difference ◽

Her2 Positive ◽

Ki 67 ◽

Hormone Receptor Positive ◽

Somatic Alteration

This study aimed to clarify the genetic difference between Korean triple-negative breast cancer (TNBC) and other breast cancer (BC) subtypes. TNBC was defined as the absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2) amplification. DNA panel of the Ion Torrent Oncomine Comprehensive Assay (OCA) v3 was performed to identify somatic alteration in 48 specimens. In a total of 102 alterations (37 nonsense, 35 missense, 8 frameshift and 22 amplifications), 30 nucleotide alterations (24 nonsense, 1 missense, and 5 frameshift) were newly identified. The eight most commonly altered genes were PIK3CA, TP53, ERBB2, BRCA2, FANCD2, AKT1, BRCA1, and FANCA. TNBC had significantly lower mutation frequency in PIK3CA (TNBC vs. hormone receptor-positive and HER2-negative BC [HRPBC], p = 0.009), but higher mutation frequency in TP53 (TNBC vs. HRPBC, p = 0.036; TNBC vs. hormone receptor-positive and HER2- positive BC [HHPBC], p = 0.004). TNBC showed frequently higher Ki-67 expression than any positive BC (p = 0.004) due to HRPBC (p < 0.001). TNBC with high Ki-67/unmutated PIK3CA/mutated TP53 appears at a younger age (52.2 ± 7.6 years), compared to other subtypes (63.7 ± 11.0 years). TNBC with high Ki-67/unmutated PIK3CA/mutated TP53 may be related to relatively early onset BCThese findings demonstrate the genomic heterogeneity between TNBC and other BC subtypes and could present a new approach for molecular targeted therapy in TNBC patients.

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Development of prognostic nomograms using institutional data for patients with triple-negative breast cancer

Future Oncology ◽

10.2217/fon-2021-0677 ◽

2021 ◽

Author(s):

Jie-Yu Zhou ◽

Kang-Kang Lu ◽

Wei-Da Fu ◽

Hao Shi ◽

Jun-Wei Gu ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Predictive Accuracy ◽

Area Under The Curve ◽

Disease Free Survival ◽

Discriminative Ability ◽

Free Survival ◽

Disease Free

Background: Triple-negative breast cancer (TNBC) is an aggressive disease. Nomograms can predict prognosis of patients with TNBC. Methods: A total of 745 eligible TNBC patients were recruited and randomly divided into training and validation groups. Endpoints were disease-free survival and overall survival. Concordance index, area under the curve and calibration curves were used to analyze the predictive accuracy and discriminative ability of nomograms. Results: Based on the training cohort, neutrophil-to-lymphocyte ratio, positive lymph nodes, tumor size and tumor-infiltrating lymphocytes were used to construct a nomogram for disease-free survival. In addition, age was added to the overall survival nomogram. Conclusion: The current study developed and validated well-calibrated nomograms for predicting disease-free survival and overall survival in patients with TNBC.

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Abstract PD1-06: Trilaciclib improves overall survival when given with gemcitabine/carboplatin in patients with metastatic triple-negative breast cancer: Final analysis of a randomized phase 2 trial

10.1158/1538-7445.sabcs20-pd1-06 ◽

2021 ◽

Author(s):

Joyce O'Shaughnessy ◽

Gail S Wright ◽

Anu R Thummala ◽

Michael A Danso ◽

Lazar Popovic ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Final Analysis ◽

Phase 2 ◽

Phase 2 Trial ◽

Randomized Phase 2

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Retrospective Study about the Prevalence of (TILs) Tumor Infiltrating Lymphocytes in Non-Metastatic Triple Negative Breast Cancer Patients and its Prognostic Value

QJM ◽

10.1093/qjmed/hcab103.003 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Hesham Ahmed ElGhazaly ◽

Manal Mohamed El-Mahdy ◽

Azza Mohamed Adel ◽

Nermeen Mostafa ◽

Aya Magdy Kamal Ali

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Retrospective Study ◽

Triple Negative Breast Cancer ◽

Prognostic Value ◽

Triple Negative ◽

Free Survival ◽

Female Patients ◽

Risk Of Death ◽

Reduced Risk

Abstract Background TNBC comprises a distinct disease entity with a unique microenvironment of TILs, the immunogenic potential of TNBC is derived from its genetic instability and high mutation rate. Tumors from patients with TNBC are more likely than tumors from patients with other subtypes to exhibit chromosomal instability and potential mutations. Objectives The study aims to evaluate the prevalence of CD8+ TILs biomarker by IHC in triple negative breast cancer and its prognostic value. TILs are an important prognostic value for the response of patient to chemotherapy the greater number of TILS is associated with higher probability of response to chemotherapy also decrease recurrence. TILS in triple negative breast cancer suggest a likely option for immunotherapy in this disease. Patients and Methods This is a retrospective study, which was carried on 30 female patients, Clinical data and paraffin wax block of female patients with triple negative breast cancer are to be collected from the breast cancer unit, department of clinical Oncology and Nuclear medicine Ain Shams university and Matarya teaching hospital. Results Several large systematic reviews and meta-analyses have confirmed that high levels of TILs are associated with better disease free survival and overall survival only in triple negative and HER2 positive subtypes, with no significant benefit seen in estrogen receptor positive breast carcinoma. In the Breast International Group (BIG) 02-98 trial shows that for every 10% increase in the intertumoral TILs there was a 17% reduced risk of relapse, and 27% reduced risk of death regardless of chemotherapy type. Also in eastern cooperative oncology group trial (ECOG) 2197, and 1199 showed that for every 10% increase in TILs, a 14% reduction of risk of recurrence, and 19% reduction in risk of death were observed. Conclusion Our study showed that All our patients (100%) were positive for CD8+, with a minimum range of 1% and a maximum range of 60%, most of the patients (20 patients) had CD8% between (10% to 20%). High levels of CD8 + TILs are good prognostic indicators in TNBC. our study showed that there were associations of CD8+ TILs infiltrate status with longer progression free survival and better overall survival in triple-negative breast cancer, but were not statistically significant probably due to our small sample size.

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